Cfdna

The diagnosis and classification of glioma by liquid biopsy represents a critical unmet need in neuro oncology. A recent study demonstrates targeted next generation sequencing (NGS) of cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) as an evolving option for liquid biopsy in patients with glioma.

Cell-free DNA (cfDNA) has long been established as a useful diagnostic and prognostic tool in a variety of clinical settings, ranging from infectious to cardiovascular and neoplastic diseases. However, non-neoplastic diseases can act as confounders impacting on the amount of cfDNA shed in bloodstream and on technical feasibility of tumour derived free circulating nucleic acids selecting patients with cancer. Here, we investigated the potential impact of other pathological processes in the clinical stratification of 637 FIT+ patients...

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour. The average survival time for a patient diagnosed with GBM, using standard treatment methods, is several months. Authors of the article pose a direct question: Is it possible to treat GBM solely with radioactive iodine (¹³¹I) therapy without employing the sodium iodide symporter (NIS) gene? After all, NIS has been detected not only in the thyroid but also in various tumours. The main author of this article (A.C.), with the assistance of her colleagues (physicians and pharmacologists), underwent ¹³¹I therapy after prior iodine inhibition, resulting in approximately 30% reduction in tumour size as revealed by magnetic resonance imaging (MRI)...

Cell-free DNA (cfDNA) is increasingly recognized as a promising biomarker candidate for disease monitoring. However, its utility in neurodegenerative diseases, like amyotrophic lateral sclerosis (ALS), remains underexplored. Existing biomarker discovery approaches are tailored to a specific disease context or are too expensive to be clinically practical. Here, we address these challenges through a new approach combining advances in molecular and computational technologies. First, we develop statistical tools to select tissue-informative DNA methylation sites relevant to a disease process of interest...

Advancements in genomic technologies have shown remarkable promise for improving health trajectories. The Human Genome Project has catalyzed the integration of genomic tools into clinical practice, such as disease risk assessment, prenatal testing and reproductive genomics, cancer diagnostics and prognostication, and therapeutic decision making. Despite the promise of genomic technologies, their full potential remains untapped without including individuals of diverse ancestries and integrating social determinants of health (SDOHs)...

PURPOSE: RAS (KRAS/NRAS) mutational status on a tumor biopsy is mandatory to guide the best treatment in metastatic colorectal cancer (mCRC). Determining the RAS mutational status by tumor-tissue biopsy is essential in guiding the optimal treatment decision for mCRC. RAS mutations are negative predictive factors for the use of EGFR monoclonal antibodies. Cell-free DNA (cfDNA) analysis enables minimally invasive monitoring of tumor evolution. METHODS/PATIENTS: PERSEIDA was an observational, prospective study assessing cfDNA RAS, BRAF and EGFR mutations (using Idylla™) in first-line mCRC, RAS wild-type (baseline tumor-tissue biopsy) patients (cohort 2)...

BACKGROUND: The Inspiration4 (I4) mission, the first all-civilian orbital flight mission, investigated the physiological effects of short-duration spaceflight through a multi-omic approach. Despite advances, there remains much to learn about human adaptation to spaceflight's unique challenges, including microgravity, immune system perturbations, and radiation exposure. METHODS: To provide a detailed genetics analysis of the mission, we collected dried blood spots pre-, during, and post-flight for DNA extraction...

Cancers of Unknown Primary (CUP) remains a diagnostic and therapeutic challenge due to biological heterogeneity and poor responses to standard chemotherapy. Predicting tissue-of-origin (TOO) molecularly could help refine this diagnosis, with tissue acquisition barriers mitigated via liquid biopsies. However, TOO liquid biopsies are unexplored in CUP cohorts. Here we describe CUPiD, a machine learning classifier for accurate TOO predictions across 29 tumour classes using circulating cell-free DNA (cfDNA) methylation patterns...

Trisomy 20 has been shown to be one of the most frequent rare autosomal trisomies in patients that undergo genome-wide noninvasive prenatal testing. Here, we describe the clinical outcomes of cases that screened positive for trisomy 20 following prenatal genome-wide cell-free (cf.) DNA screening. These cases are part of a larger cohort of previously published cases. Members of the Global Expanded NIPT Consortium were invited to submit details on their cases with a single rare autosomal aneuploidy following genome-wide cfDNA screening for retrospective analysis...

Colorectal cancer (CRC) is a significant global health concern. We need ways to detect it early and determine the best treatments. One promising method is liquid biopsy, which uses cancer cells and other components in the blood to help diagnose and treat the disease. Liquid biopsies focus on three key elements: circulating tumor DNA (ctDNA), circulating microRNA (miRNA), and circulating tumor cells (CTC). By analyzing these elements, we can identify CRC in its early stages, predict how well a treatment will work, and even spot signs of cancer returning...

OBJECTIVE: 22q11.2 deletion syndrome (DS) is a serious condition with a range of features. The small microdeletion causing 22q11.2DS makes it technically challenging to detect using standard prenatal cfDNA screening. Here, we assess 22q11.2 microdeletion clinical performance by a prenatal cfDNA screen that incorporates fetal fraction (FF) amplification. METHODS: The study cohort consisted of patients who received Prequel (Myriad Genetics, Inc.), a prenatal cfDNA screening that incorporates FF amplification, and met additional eligibility criteria...

OBJECTIVE: Determine current analytical methods and number of cell-free (cf) DNA prenatal screening tests performed for common trisomies. METHODS: The College of American Pathologists 2022-B Noninvasive Prenatal Testing exercise was distributed in December 2022 to 93 participants in 22 countries. Supplemental questions included the number of tests performed in a recent month and the proportion of samples originating outside the United States (US). RESULTS: Eighty-three participants from three continents returned results; 74 (89%) were suitable for the analyses...

Large-scale copy number variants (CNVs) are structural alterations in the genome that involve the duplication or deletion of DNA segments, contributing to genetic diversity and playing a crucial role in the evolution and development of various diseases and disorders, as they can lead to the dosage imbalance of one or more genes. Massively parallel sequencing (MPS) has revolutionized the field of genetic analysis and contributed significantly to routine clinical diagnosis and screening. It offers a precise method for detecting CNVs with exceptional accuracy...

Post-transplant complications reduce allograft and recipient survival. Current approaches for detecting allograft injury non-invasively are limited and do not differentiate between cellular mechanisms. Here, we monitor cellular damages after liver transplants from cell-free DNA (cfDNA) fragments released from dying cells into the circulation. We analyzed 130 blood samples collected from 44 patients at different time points after transplant. Sequence-based methylation of cfDNA fragments were mapped to patterns established to identify cell types in different organs...

Alopecia areata (AA) is an autoimmune disease characterized by damage to hair follicles and hair loss. Cell-free DNA (cfDNA) has recently received attention as a biomarker of various disorders including inflammatory skin diseases. In this study, we aimed to investigate the clinical significance of cfDNA and the circulating DNAs of disease-associated cytokines in AA patients. Serum samples were obtained from 63 patients with AA and 32 healthy controls (HC). Using droplet digital polymerase chain reaction, circulating C-X-C motif chemokine ligand (CXCL) 9, CXCL10, CXCL11, C-X-C motif chemokine receptor 3, interferon (IFN)-γ, interleukin (IL) -7, IL-15, and Janus kinase (JAK) 2 were detectable in both HC and AA patients...

A better understanding of the function of neutrophil extracellular traps (NETs) may facilitate the development of interventions for sepsis. The study aims to investigate the formation and degradation of NETs in three murine sepsis models and to analyze the production of reactive oxygen species (ROS) during NET formation. Murine sepsis was induced by midgut volvulus (720° for 15 min), cecal ligation and puncture (CLP), or the application of lipopolysaccharide (LPS) (10 mg/kg body weight i.p.). NET formation and degradation was modulated using mice that were genetically deficient for peptidyl arginine deiminase-4 (PAD4 -KO) or DNase1 and 1L3 (DNase1/1L3 -DKO)...

Currently, there are no reliable prognostic factors to determine which upper tract urothelial carcinoma (UTUC) patients will progress after radical nephroureterectomy (RNU). We aim to evaluate whether liquid-biopsy-based biomarkers (circulating tumor cells (CTCs), cell-free DNA (cfDNA), and circulating tumor DNA (ctDNA)) were able to predict clinical outcomes in localized UTUC patients undergoing RNU. Twenty patients were prospectively enrolled between 2021 and 2023. Two blood samples were collected before RNU and three months later...

Current prostate carcinoma (PCa) biomarkers, including total prostate-specific antigen (tPSA), have unsatisfactory diagnostic sensitivity and specificity resulting in overdiagnosis and overtreatment. Previously, we described an optimised bias-based preamplification-digital droplet PCR (OBBPA-ddPCR) technique, which detects tumour DNA in blood-derived cell-free DNA (cfDNA) of cancer patients. The current study investigated the performance of newly developed OBBPA-ddPCR-based biomarkers. Blood plasma samples from healthy individuals ( n = 90, controls) and PCa ( n = 39) and benign prostatic hyperplasia patients (BPH, n = 40) were analysed...

Bladder cancer (BC) is one of the most common malignancies in the United States, with over 80,000 new cases and 16,000 deaths each year. Urothelial carcinoma (UC) is the most common histology and accounts for 90% of cases. BC management is complicated by recurrence rates of over 50% in both muscle-invasive and non-muscle-invasive bladder cancer. As such, the American Urological Association (AUA) recommends that patients undergo close surveillance during and after treatment. This surveillance is in the form of cystoscopy or imaging tests, which can be invasive and costly tests...

We aimed to study the incidence and genomic spectrum of actionable alterations (AA) detected in serial cfDNA collections from patients with metastatic breast cancer (MBC). Patients with MBC who underwent plasma-based cfDNA testing (Guardant360® ) between 2015 and 2021 at an academic institution were included. For patients with serial draws, new pathogenic alterations in each draw were classified as actionable alterations (AA) if they met ESCAT I or II criteria of the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT)...